精神分裂症患者血浆外泌体微小RNA差异表达谱及其生物信息学分析  

Differential expression profile and bioinfomatic analysis of plasma exosomal miRNA in schizophrenia

作　　者：梁静文 余卓恒 刘宜欢 叶彩虹 许瑞环 LIANG Jing-wen;YU Zhuo-heng;LIU Yi-huan;YE Cai-hong;Xu Rui-huan(Clinical Laboratory,Longgang Distric Central Hospital,Shenzhen 518172,China)

机构地区：[1]深圳市龙岗中心医院检验科,518172 [2]北京中医药大学深圳医院(龙岗) [3]深圳市康宁医院检验科 [4]香港中文大学(深圳)附属第二医院

出　　处：《临床精神医学杂志》2023年第5期372-376,共5页Journal of Clinical Psychiatry

基　　金：深圳市龙岗区2019年度医疗卫生科技计划项目(LGKCYLWS2019000334)。

摘　　要：目的:探讨精神分裂症患者及正常人群血浆外泌体微小RNA(miRNA)的差异表达,初步了解差异表达miRNA在精神分裂症病程发展中的作用。方法:采用高通量测序技术检测48例精神分裂症患者和48名健康对照者的血浆外泌体miRNA的表达水平,构建miRNA差异表达谱。预测表达差异显著的miRNA的靶基因,再对靶基因进行GO功能注释和KEGG通路分析,确定差异表达miRNA的主要生物学功能及其可能参与的信号通路。结果:与对照组相比,精神分裂症患者血浆外泌体共筛选出353个miRNA显著异常表达,其中157个表达上调,196个表达下调。通过GO富集和KEGG分析,上述差异表达的miRNAs主要涉及神经元细胞体、谷氨酸能突触、神经元间突触、突触前和突触膜等细胞组成,并主要参与轴突新生、化学突触传递调节、跨突触信号调节等生物过程,可能通过MAPK信号通路、PI3K Akt信号通路、TNF信号通路、Wnt信号通路、FoxO信号通路、多巴胺能突触及Hippo等信号通路参与精神分裂症的发生和发展过程。结论:经药治疗精神分裂症患者血浆外泌体中miRNAs存在显著的差异性表达,miRNA-206、miR-142-5p、miR-139-5p、miR-133b等miRNA可能通过MAPK信号通路、PI3K Akt信号通路等在精神分裂症的发生发展过程中发挥重要作用。Objective:To explore the differential expression of plasma exosomal microRNA in the schizophrenic patients and normal population individuals,and to understand the role of differentially expressed miRNA in the progression of schizophrenia.Method:High-throughput sequencing technology was used to detect the expression levels of exosomal miRNA in plasma samples from 48 schizophrenic patients by medication and 48 healthy controls,and to construct miRNA differential expression level.Predict target genes of differentially expressed miRNAs and then Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed on the target genes,determine the major biological functions of differentially expressed miRNA and their possible signaling pathways.Results:Compared with normal individuals,there were 353 significantly differentially expressed miRNAs in plasma of schizophrenic patients,of which 157 were up-regulated and 196 down-regulated.Through GO enrichment and KEGG analysis,the miRNAs involved in neuronal cell body,glutamatergic synapse,presynapse,synaptic membrane,neuron to neuron synapse and other cellular components,and participated in multiple biological processes such as axonogenesis,modulation of chemical synaptic transmission and regulation of trans-synaptic signaling.Moreover,the miRNAs may participated in the occurrence and development of schizophrenia through MAPK signaling pathway,PI3K Akt signaling pathway,TNF signaling pathway,Wnt signaling pathway,FoxO signaling pathway,dopaminergic synapse signaling pathway and Hippo signaling pathway.Conclusion:The significant difference in the expressions of plasma exosomal microRNA in schizophrenic patients with medication treatments indicated that miRNAs such as miRNA-206,miR-142-5p,miR-139-5p and miR-133b may play an important role in the occurrence and development of schizophrenia through MAPK signaling pathway and PI3K Akt signaling pathway.

关 键 词：精神分裂症 血浆 外泌体 微小RNA 生物信息学分析 

分 类 号：R749.4[医药卫生—神经病学与精神病学]